INTRODUCTION: Barrett's esophagus is a metaplastic lesion. However, the cellular and molecular mechanisms involved are poorly understood. The aim of this study was to investigate the roles of KLF4 and BMP4 in the pathogenesis of Barrett's epithelium. MATERIALS AND METHODS: Immunohistochemistry was used to analyse the expression of KLF4, BMP4, CDX2, MUC2 and MUC5AC in human esophageal specimens. Human esophageal squamous epithelial cells were subjected to bile acid treatment and used in transfection experiments. Quantitative real-time PCR and Western blot analysis were used to detect the expression of KLF4, BMP4, CDX2, MUC2 and MUC5ac. RESULTS: In human tissues, Barrett's epithelium strongly expressed BMP4, p-Smad1/5/8 and KLF4. Furthermore, bile acids increased the expression of BMP4, KLF4, p-Smad1/5/8, CDX2, MUC2 and MUC5ac in esophageal epithelial cells in a time-dependent manner. Moreover, we found that BMP4 up-regulated the expression of KLF4, CDX2, MUC2 and MUC5ac, but Noggin, a specific BMP4 antagonist, can block the expression of KLF4, CDX2, MUC2 and MUC5ac induced by BMP4. However, BMP4 cannot induce the expression of CDX2, MUC2 and MUC5ac in cells with KLF4 siRNA, and Noggin cannot block the expression of KLF4, CDX2, MUC2 and MUC5ac in cells transfected with the KLF4 expression vector. CONCLUSION: Our results demonstrate that BMP4 promotes a phenotype change of an esophageal squamous epithelium via up-regulation of KLF4.
INTRODUCTION: Barrett's esophagus is a metaplastic lesion. However, the cellular and molecular mechanisms involved are poorly understood. The aim of this study was to investigate the roles of KLF4 and BMP4 in the pathogenesis of Barrett's epithelium. MATERIALS AND METHODS: Immunohistochemistry was used to analyse the expression of KLF4, BMP4, CDX2, MUC2 and MUC5AC in human esophageal specimens. Human esophageal squamous epithelial cells were subjected to bile acid treatment and used in transfection experiments. Quantitative real-time PCR and Western blot analysis were used to detect the expression of KLF4, BMP4, CDX2, MUC2 and MUC5ac. RESULTS: In human tissues, Barrett's epithelium strongly expressed BMP4, p-Smad1/5/8 and KLF4. Furthermore, bile acids increased the expression of BMP4, KLF4, p-Smad1/5/8, CDX2, MUC2 and MUC5ac in esophageal epithelial cells in a time-dependent manner. Moreover, we found that BMP4 up-regulated the expression of KLF4, CDX2, MUC2 and MUC5ac, but Noggin, a specific BMP4 antagonist, can block the expression of KLF4, CDX2, MUC2 and MUC5ac induced by BMP4. However, BMP4 cannot induce the expression of CDX2, MUC2 and MUC5ac in cells with KLF4 siRNA, and Noggin cannot block the expression of KLF4, CDX2, MUC2 and MUC5ac in cells transfected with the KLF4 expression vector. CONCLUSION: Our results demonstrate that BMP4 promotes a phenotype change of an esophageal squamous epithelium via up-regulation of KLF4.